Prostaglandins have been classified into two large series which differ from each other in having in one case (PGF) two hydroxyl groups in the 5 atom carbon ring, and in the other case (PGE) a ketone group and a hydroxyl group in the same ring. There are also sub-classes characterized by the presence of a double bond in a determined position or by the presence of several double bonds.
As stated, prostaglandins are formed in the organism by biosynthesis from polyunsaturated fatty acids containing 20 carbon atoms, and essentially 8,11,14-eicosatrienoic acid, 5,8,11,14-eicosatetraenoic acid, and 5,8,11,14,17-eicosapentenoic acid, which are liberated by an enzymatic process from the lipids present in an organism. Recent studies on prostaglandins have shown that these substances are responsible in the organism for a large number of biological mechanisms extending from fertility control to stimulating smooth musculature contractions, and influencing arterial tension, platelet aggregation, muscular and articular pains etc.
In practice, the large amount of work carried out has shown that the prostaglandins are of considerable use in solving the problem of birth control, by administration in doses sufficient to induce abortion.
However, the high hopes raised in this field have largely disappeared, and work on the practical use of prostaglandins has come to a sudden halt following the established appearance of side effects which it has not been possible to eliminate or control.
In this respect, it has been found that in order to obtain the desired fertility control or to induce abortion it is necessary to administer prostaglandins in such large doses that the other biological processes initiated by prostaglandins come into being, with the risk of inducing arterial hypertension, intestinal muscular contraction with vomit and diarrhoea, hemicrania, reduction in the pain threshold in muscles and joints, hyperthermia and platelet aggregation.
In a previous patent application (Italian application No. 28419 A/74) by the same inventors, high vinyl polymers containing radicals of prostaglandins or of their precursor fatty acids have been described.
These polymers, which may be used in human therapy in all fields in which prostaglandins are used, have the great advantage relative thereto of permitting controlled continuous feeding of prostaglandins, so avoiding the administration of large doses and the consequent heavy side effects. However, in continued experiments, certain important facts have emerged.
(1) The administration of polymers containing precursor fatty acids is preferable to the administration of polymers containing prostaglandin radicals in that the organism is able to utilize the specific biosynthetic enzymes of the prostaglandins and respect the differences between organs and tissues in the production of the specific endogenous prostaglandins required by the organism.
In contrast, the indiscriminate administration of a single specific synthesis prostaglandin can create unbalance in determined organs and/or tissues.
(2) The use of polymers containing prostaglandin precursor acid radicals is preferable to the use of polymers containing the prostaglandin radicals themselves in that where there is an unexpected or toxic reaction in the individual or animal, this may be immediately blocked by administering specific prostaglandin synthesis inhibitors such as acetylsalicylic acid, indomethacin and the like. This is evidently not possible when administering polymers directly containing the synthesic prostaglandins.
(3) While the use of macromolecular polyvinyl matrix polymers is satisfactory in oral or intra-uterine administration, in the case of parenteral administration it has been found that the vinyl polymer residue after separation of the prostaglandin or acid radicals is not degraded and thus eliminated from the organism, but tends to accumulate. This means that parenteral administration, which is highly desirable or even necessary in many cases, cannot be attained with these polymers, which constitutes a serious limitation to the use of the drugs.
(4) In an attempt to solve the aforesaid problems, the direct administration of the polyunsaturated aliphatic acid precursors of prostaglandins in the pure state has been considered. However, it has been found that acids thus administered become metabolised by the organism in a few minutes, to form only traces of prostaglandins.